|Publication Type||Journal Article|
|Year of Publication||2008|
|Authors||Hoshida, Y, Villanueva, A, Kobayashi, M, Peix, J, Chiang, DY, Camargo, A, Gupta, S, Moore, J, Wrobel, MJ, Lerner, J, Reich, M, Chan, JA, Glickman, JN, Ikeda, K, Hashimoto, M, Watanabe, G, Daidone, MG, Roayaie, S, Schwartz, M, Thung, S, Salvesen, HB, Gabriel, S, Mazzaferro, V, Bruix, J, Friedman, SL, Kumada, H, Llovet, JM, Golub, TR|
|Journal||N Engl J Med|
|Date Published||2008 Nov 06|
|Keywords||Aged, Carcinoma, Hepatocellular, Feasibility Studies, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genome-Wide Association Study, Humans, Liver, Liver Neoplasms, Male, Middle Aged, Multivariate Analysis, Neoplasm Recurrence, Local, Oligonucleotide Array Sequence Analysis, Paraffin Embedding, Polymerase Chain Reaction, Prognosis, Survival Analysis, Tissue Fixation|
BACKGROUND: It is a challenge to identify patients who, after undergoing potentially curative treatment for hepatocellular carcinoma, are at greatest risk for recurrence. Such high-risk patients could receive novel interventional measures. An obstacle to the development of genome-based predictors of outcome in patients with hepatocellular carcinoma has been the lack of a means to carry out genomewide expression profiling of fixed, as opposed to frozen, tissue.
METHODS: We aimed to demonstrate the feasibility of gene-expression profiling of more than 6000 human genes in formalin-fixed, paraffin-embedded tissues. We applied the method to tissues from 307 patients with hepatocellular carcinoma, from four series of patients, to discover and validate a gene-expression signature associated with survival.
RESULTS: The expression-profiling method for formalin-fixed, paraffin-embedded tissue was highly effective: samples from 90% of the patients yielded data of high quality, including samples that had been archived for more than 24 years. Gene-expression profiles of tumor tissue failed to yield a significant association with survival. In contrast, profiles of the surrounding nontumoral liver tissue were highly correlated with survival in a training set of tissue samples from 82 Japanese patients, and the signature was validated in tissues from an independent group of 225 patients from the United States and Europe (P=0.04).
CONCLUSIONS: We have demonstrated the feasibility of genomewide expression profiling of formalin-fixed, paraffin-embedded tissues and have shown that a reproducible gene-expression signature correlated with survival is present in liver tissue adjacent to the tumor in patients with hepatocellular carcinoma.
|Alternate Journal||N. Engl. J. Med.|
|PubMed Central ID||PMC2963075|
|Grant List||1R01DK076986-01 / DK / NIDDK NIH HHS / United States |
5U54 CA112962-03 / CA / NCI NIH HHS / United States
R01 DK037340-14 / DK / NIDDK NIH HHS / United States
R01 DK076986 / DK / NIDDK NIH HHS / United States
DK37340 / DK / NIDDK NIH HHS / United States
R01 DK076986-01 / DK / NIDDK NIH HHS / United States
U54 CA112962 / CA / NCI NIH HHS / United States
U54 CA112962-03 / CA / NCI NIH HHS / United States
R01 DK037340 / DK / NIDDK NIH HHS / United States